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BackgroundTo collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial.MethodsTwenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT).ResultsRMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine.ConclusionsThe relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.

Purpose Dysphagia is a common symptom experienced by patients with motor neuron disease (MND). The Yale Swallow Protocol (YSP) is a validated screening instrument for identifying patients at risk for aspiration. The purpose of this exploratory cross-sectional, multicenter study was to investigate how the YSP results in identifying aspiration risk in patients with MND in comparison with aspiration observed during a videofluoroscopic swallow study (VFSS). Method Participants referred for VFSS as part of clinical management were recruited from four specialized MND clinics. All participants were administered the YSP immediately prior to the VFSS by a speech-language pathologist, with results recorded as pass or fail. Aspiration on VFSS was determined using the Penetration-Aspiration Scale (scores 6-8). A 2 × 2 contingency table was constructed to compare results of YSP with those on VFSS. Results Thirty-one patients with MND (13 males, 18 females; M age = 64 ± 12 years) referred for VFSS participated in this study. Of the 22 patients who failed the YSP, interrupted drinking was the most frequent reason (65%). Compared to the VFSS, the YSP yielded a sensitivity of 80%, a specificity of 33%, positive predictive value of 36%, and negative predictive value of 78%. Conclusions The YSP is a simple tool and easy to utilize and has a high sensitivity in identifying aspiration risk in amyotrophic lateral sclerosis. A future investigation with a larger sample size is needed to better investigate the utility of YSP as a screening tool for this population.